neurotropic virusBS are a major cause of morbidity and mortality worldwide, the proposed program is designed to develop investigators derived from 2 sources: (a) PHYSICIANS, with prior training in neurology (including pediatric neurology), pediatrics or neuropathology;and (b) PhDs, with a background in virology or molecular biology. The goal is to steer them into problems in neurological disease which can be attacked by these disciplines. This is a laboratory research training program which includes experience with important methods in virology and molecular biology. The disciplines currently being used are protein purification and nucleic acid hybridization, molecular genetics, production and characterization of cDNA libraries, DNA sequencing, molecular cloning, virology, production of monoclonal and polyclonal antibodies, cell sorting, quantization of humoral and cell-mediated immune responses, preparation of subunit viral vaccine and its expression, and molecular aspects of viral pathogenesis. Each trainee. In collaboration with one of 9 experienced trainers, undertakes an independent study over a 3-year period, which provides experience in the design and analysis of experiments, and in the presentation and publication of results. Weekly formal meetings and presentations provide constant interchange between trainees and frequent exposure to many trainers. Research is also often supplemented by formal courses and informal seminars. This training program builds on several strengths: (a) well-established Graduate Faculty in Microbiology & Immunology and in Molecular Biology which grant the PhD degree;(b) an NIH-funded Neuroscience Center of Excellence;(c) a cadre of investigators at the Univ. Colo. School of Medicine and at the Eleanor Roosevelt Institute at the Univ. Denver with proven track records and commitment to research in neurovirology and the molecular biology of neurologic disease;(d) 3 NIH-supported program project grants focused on neurologic disease produced by neurotropic virus infection, and by somatic or mitochondrial DNA defects;and (e) considerable individual experience of the trainers with postdoctoral fellows as detailed in the body of this proposal. Training facilities for programs are extensive not only within immediate surroundings of the individual trainer's laboratories, but also extend to collaborating laboratories at the U. Colo. School of Medicine when necessary. Laboratories are well equipped for biochemical, molecular biological, immunological, genetic and neuroscience investigations. Upon completion, postdoctorals are qualified to begin junior faculty positions as independent investigators to study neurovirologic or molecular biologic aspects of neurologic diseases. The training program in Neurovirology-Molecular Biology at the Univ. Colo. School of Medicine has been successfully training 4 postdoctoral fellows a year for the past 20 years. RELEVANCE: Neurological diseases caused by highly neurotropic viruses are a major cause of morbidity and mortality worldwide. Just a few examples include the HIV virus that causes AIDS, as well as multiple herpes viruses, enteroviruses (formerly polio and now the Coxsackie and ECHO viruses), and the Togaviruses (the viruses that cause Eastern, Western and Venezuelan Equine encephalitis) and various Flaviviruses (most notably West Nile Virus). Analysis of the clinical features and molecular mechanisms by which these viruses produce neurological disease is essential to the eventual prevention and treatment of neurological deficit and death produced by these viruses.